1-(2-Hydroxyethyl)piperazine → 1-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)piperazine

HRID 79151Notes

Reaction equation

HRID 79151 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[Si:10](Cl)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]>ClCCl>[CH3:14][C:13]([Si:10]([CH3:12])([CH3:11])[O:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:16])[CH3:15]

Participants

4

Reactant 2

HCID 76771-(2-Hydroxyethyl)piperazineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 582998241-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)piperazineYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 1-(2-hydroxyethyl)-piperazine (3.36 g, 25.8 mmol) in dichloromethane (25 mL) was added tert-butyldimethylsilylchloride (3.89 g, 25.8 mmol). The reaction mixture was stirred at room temperature. The reaction mixture was stirred overnight, then diluted 1× with CH2Cl2 and extracted against 0.5 N NaOH (100 mL). The aqueous was extracted further with 10% methanol in CH2Cl2 (3×100 mL). The combined organics were dried with Na2SO4 and concentrated in vacuo. Silica gel chromatography (gradient elution 0 to 100% B (7% methanol in DCM+1% NH4OH additive) against A (3% methanol in DCM+0.175% NH4OH additive) afforded compound 246 (4.71 g, 74.7% yield). 1H NMR (500 MHz, CDCl3) δ 0.06 (s, 6 H) 0.90 (s, 9 H) 2.36-2.59 (m, 6 H) 2.89 (t, J=4.77 Hz, 4 H) 3.76 (t, J=6.48 Hz, 2 H) ppm.

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. extractionextracted against 0.5 N NaOH (100 mL)
  3. extractionThe aqueous was extracted further with 10% methanol in CH2Cl2 (3×100 mL)
  4. dry with materialThe combined organics were dried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. washSilica gel chromatography (gradient elution 0 to 100% B (7% methanol in DCM+1% NH4OH additive) against A (3% methanol in DCM+0.175% NH4OH additive)

Sources & evidence

ORD record
ord-f7c88150054a4d60992397e5fa68fcb4
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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